This invention relates to the regulation of blood pressure, and particularly to apparatus and methods for the continuous regulation of blood pressure by controlled infusion of drugs which combat hypertension and hypotension.
Several drugs are known and commercially available which when administered in proper dosages have the primary effect of regulating the blood pressure. As is set forth in greater detail hereinafter, such drugs may be used either to alter cardiac output (either by changing the capacity of the heart or intravascular volume), or to alter peripheral resistance or state of contraction of the arteriolar resistance vessels. Hypotensive agents act by reducing one or several of these parameters, and hypertensive agents result in opposite effects. In either event, the rate of onset and degree of effectiveness of drugs to achieve satisfactory pressure levels is substantially dependent upon the mode of administration and pharmacodynamics of the drug used.
Conventionally, drugs for the regulation of blood pressure are administered by continuous intravenous drip or pump, intramuscular or intravenous injection, or orally. All such methods, however, involve severe difficulties in controlling undesired rise and decay of drug concentration within the patient, which changes may be exponential in character.
It is a primary object of the present invention to provide apparatus and methods for automatically, safely, and effectively providing acute continuous blood pressure regulation through the controlled infusion of drugs.
A major class of systems attempting to achieve automated continuous control involves utilization of a computer to assume select aspects of the decision process. In such systems, a large number of measured parameters from the subject are processed logically, with the ultimate result being a decision whether and how much further infusion of drugs is presently required. Some such prior art systems are open loop and others are closed loop in function, and some work on fixed periodicity in digital fashion, while others work continuously in analog fashion. For example, in one system described by M. Schade in Technical Report 6972-2 of the Stanford University Center for Systems Research, August 1971, a computer, controller, pump, and subject with blood pressure information feedback operate independently from any manual intervention. In Schade's system, the actual blood pressure of the subject is compared with a desired pressure, and the resulting error signal is manipulated by a computer controller which models behavior of the subject and which activates a pump to infuse the appropriate amount of drug. At one point (p. 53), Schade suggests that an adaptive differential-model controller might be useful, but also notes that such an approach involves at least one weakness in that one must consider derivatives to form the model.
While interactive computer control involves extensive capacity for monitoring plural data from the subject, and multiple effects of the infused drug, such systems are unduly large, complex, and expensive for general availability. It is accordingly an object of the present invention to provide relatively simple and economical systems for the infusion of drugs to control blood pressure.
In a second class of prior art systems, fixed logic controls the rate of infusion of a blood pressure control drug in response to an error between the present pressure and a desired pressure. In one exemplary machine, as described by H. Muller and M. Stuach in Zeitsch. Biol. 116:288-290, 1969, a hypotensive state was established by infusion of phentolamine, and the blood pressure was then raised, based on proportional plus integral control, by infusion of epinephrine. In another example, commercially available Harvard Apparatus Servo Controlled Liquid Pumping System, Model 990, Millis, Mass., which is discussed in greater detail hereinafter, the error between present and desired pressure is manipulated by a proportionality factor, whereupon a pump is operated to alter infusion rates. Both of the foregoing examples in the latter class involve serious deficiencies. In the former, the pressure reduction-increase procedure tends to involve steady state errors, and furthermore tends to be quite slow to respond. In the latter case, the degree of control achieved is inadequate, with resultant variation and overshoot in pressure.
It is accordingly a further object of the present invention to provide closed loop control whereby the blood pressure is brought to the desired level speedily and without substantial danger of overshoot of the desired level.